EBF2 determines and maintains brown adipocyte identity

Sona Rajakumari, Jun Wu, Jeff Ishibashi, Hee Woong Lim, An Hoa Giang, Kyoung Jae Won, Randall R. Reed, Patrick Seale

Research output: Contribution to journalArticle

Abstract

The master transcription factor Pparγ regulates the general differentiation program of both brown and white adipocytes. However, it has been unclear whether Pparγ also controls fat lineage-specific characteristics. Here, we show that early B cell factor-2 (Ebf2) regulates Pparγ binding activity to determine brown versus white adipocyte identity. The Ebf DNA-binding motif was highly enriched within brown adipose-specific Pparγ binding sites that we identified by genome-wide ChIP-Seq. Of the Ebf isoforms, Ebf2 was selectively expressed in brown relative to white adipocytes and was bound at brown adipose-specific Pparγ target genes. When expressed in myoblasts or white preadipose cells, Ebf2 recruited Pparγ to its brown-selective binding sites and reprogrammed cells to a brown fat fate. Brown adipose cells and tissue from Ebf2-deficient mice displayed a loss of brown-specific characteristics and thermogenic capacity. Together, these results identify Ebf2 as a key transcriptional regulator of brown fat cell fate and function.

Original languageEnglish (US)
Pages (from-to)562-574
Number of pages13
JournalCell Metabolism
Volume17
Issue number4
DOIs
StatePublished - Apr 2 2013

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Rajakumari, S., Wu, J., Ishibashi, J., Lim, H. W., Giang, A. H., Won, K. J., Reed, R. R., & Seale, P. (2013). EBF2 determines and maintains brown adipocyte identity. Cell Metabolism, 17(4), 562-574. https://doi.org/10.1016/j.cmet.2013.01.015